Fabry disease: development and progression of left ventricular hypertrophy despite long-term enzyme replacement therapy

Background Enzyme replacement therapy (ERT) may halt or attenuate disease progression in patients with Anderson-Fabry disease (AFD). However, whether left ventricular hypertrophy (LVH) can be prevented by early therapy or may still progress despite ERT over a long-term follow-up is still unclear. Methods Consecutive patients with AFD from the Independent Swiss-Fabry Cohort receiving ERT who were at least followed up for 5 years were included. Cardiac progression was defined as an increase of >10 g/m 2 in left ventricular mass index (LVMI) between the first and the last available follow-up transthoracic echocardiography. Results 60 patients (35 (23–48) years, 39 (65%) men) were followed up for 10.5 (7.2–12.2) years. 22 had LVH at ERT start (LVMI of 150±38 g/m 2 ). During follow-up, 22 (36%, 34±15 years) had LVMI progression of 12.1 (7–17.6) g/m 2 per 100 patient-years, of these 7 (11%, 29±13 years) with no LVH at baseline. Three of them progressed to LVH. LVMI progression occurred mostly in men (17 of 39 (43%) vs 5 of 21 (24%), p10 years under ERT, 36% of the patients still had LVMI cardiac progression, and 32%, predominantly older men, experienced major AFD-related events. LVH at treatment initiation was a strong predictor of LVMI progression and adverse events on ERT.